|Lloviu virus (LLOV)|
|Group:||Group V ((-)ssRNA)|
|Species:||"Lloviu cuevavirus" (proposed)|
Use of term
Lloviu virus (abbreviated LLOV) was first mentioned in 2010 as a single member of a suggested species "Lloviu cuevavirus", which was suggested to be included into the suggested genus "Cuevavirus", family Filoviridae, order Mononegavirales. The name Lloviu virus is derived from Cueva del Lloviu, the name of a Spanish cave in which it was first discovered.
Lloviu virus is pronounced j’ɔːvjuː vaɪrəs (IPA). According to the rules for taxon naming established by the International Committee on Taxonomy of Viruses (ICTV), the name Lloviu virus is always to be capitalized (because "Lloviu" is a proper noun), but is never italicized, and may be abbreviated (with LLOV being the official abbreviation).
Virus inclusion criteria
A virus that fulfills the criteria for being a member of the species "Lloviu cuevavirus" is a Lloviu virus if it has the properties of "Lloviu cuevaviruses" and if its genome diverges from that of the prototype "Lloviu cuevavirus", Lloviu virus variant Bat86 (LLOV/Bat86), by ≤10% at the nucleotide level.
LLOV was discovered in 2002 in Schreiber's long-fingered bats (species Miniopterus schreibersii) found dead in Cueva del Lloviu, Asturias, Spain, as well as in caves in Spanish Cantabria and in caves in France and Portugal. It has not yet been proven that the virus is the etiological agent of a novel bat disease, but healthy Schreiber's long-fingered bats were not found to contain traces of the viruses, thereby at least suggesting that the virus may be pathogenic for certain bats. Necropsies of dead bats did not reveal macroscopic pathology, but microscopic examination suggested viral pneumonia. Cueva del Lloviu is frequented by tourists, yet no human infections or disease has ever been observed, suggesting that LLOV is the second filovirus not pathogenic for humans (the first one being Reston virus (RESTV)).
LLOV has yet to be isolated in tissue culture or living animals, but its genome has been determined in its entirety with exception of the 3' and 5' UTRs. Like all mononegaviruses, LLOV virions contain a non-infectious, linear nonsegmented, single-stranded RNA genome of negative polarity that most likely possesses inverse-complementary 3' and 5' termini, does not possess a 5' cap, is not polyadenylated, and is not covalently linked to a protein. The LLOV genome is probably approximately 19 kb long and contains seven genes in the order 3'-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR. In contrast to ebolaviruses and marburgviruses, which synthesize seven mRNAs to express the seven structural proteins, LLOV seems to produce only six mRNAs, i.e. one mRNA (VP24/L) is thought to be bicistronic. LLOV genomic transcriptional initiation sites are identical to those of ebolavirus genomes but different from those of marburgvirus genomes. LLOV transcriptional termination sites are unique.
The structure of LLOV virions has not yet been described. Like all other filoviruses, LLOV virions are expected to be filamentous particles that may appear in the shape of a shepherd's crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched. Their diameter is expected to be 80 nm in width, but vary in length. The LLOV genome suggests that LLOV particles consist of seven structural proteins. At the center would be the helical ribonucleocapsid, which would consist of the genomic RNA wrapped around a polymer of nucleoproteins (NP). Associated with the ribonucleoprotein would be the RNA-dependent RNA polymerase (L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein would be embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles would be surrounded by a lipid membrane derived from the host cell membrane. The membrane would anchor a glycoprotein (GP1,2) that projects 7 to 10 nm spikes away from its surface. While nearly identical to ebolavirions and marburgvirions in structure, lloviuvirions may be antigenically distinct from both (just as they are from each other).
The LLOV life cycle is hypothesized to begin with virion attachment to specific cell-surface receptors, followed by internalization, fusion of the virion envelope with endosomal membranes and the concomitant release of the virus nucleocapsid into the cytosol. LLOV glycoprotein (GP) is cleaved by endosomal cysteine proteases (cathepsins) and the cleaved glycoprotein interacts with the intracelluar entry receptor, Niemann-Pick C1 (NPC1). The virus RdRp would partially uncoat the nucleocapsid and transcribe the genes into positive-stranded mRNAs, which would then be translated into structural and nonstructural proteins. LLOV L would bind to a single promoter located at the 3' end of the genome. Transcription would either terminate after a gene or continue to the next gene downstream. This means that genes close to the 3' end of the genome would be transcribed in the greatest abundance, whereas those toward the 5' end would be least likely to be transcribed. The gene order would therefore be a simple but effective form of transcriptional regulation. The most abundant protein produced would be the nucleoprotein, whose concentration in the cell would determine when L switches from gene transcription to genome replication. Replication would result in full-length, positive-stranded antigenomes that would in turn be transcribed into negative-stranded virus progeny genome copies. Newly synthesized structural proteins and genomes would self-assemble and accumulate near the inside of the cell membrane. Virions would bud off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles would then infect other cells to repeat the cycle.
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